Germline Multigene Panel Testing in Oncology: Genetic Counseling Perspective

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1 Germline Multigene Panel Testing in Oncology: Genetic Counseling Perspective Sarah L. Campian, MS CGC Certified Genetic Counselor Nancy & James Grosfeld Cancer Genetics Center

2 Objectives Identify patients/families at risk for a hereditary cancer syndrome Describe complexities of germline panel testing for hereditary cancer, including the benefits and limitations Understand importance of obtaining adequate patient informed consent for panel testing 11/9/2015 2

3 Genetic Counseling is a Multistep Process 11/9/2015 3

4 Which Patient Should See Genetics? 11/9/2015 4

5 Which Patient Should See Genetics? 11/9/2015 5

6 Genetic Testing for Hereditary Cancer HEREDITARY 5-10% Cancer FAMILIAL 20-25% SPORADIC 70-75% 11/9/2015 6

7 Genetic Testing for Hereditary Cancer HEREDITARY 5-10% BRCA1, BRCA2 MLH1, MSH2, MSH6, PMS2, EPCAM PTEN TP53 CDH1 PALB2 CHEK2 ATM STK11 APC, MUTYH BMPR1A, SMAD4 Cancer 11/9/ AKT1, AXIN2, BAP1, BARD1, BLM, BRIP1, BUB1B, CDC73, CDK4, CDKN2A, CTNNA1, CTCRC, DICER1, EGLN1, ENG, FAM175A, FANCC, FH, FLCN, GALNT12, GREM1, KIF1B, KIT, MLH3, MRE11A, NBN, NF1, PALLD, PDGFRA, PIK3CA, POLD1, POLE, PTCH1, RAD50, RAD51C, RAD51D, RET, RINT1, SDHA, SDHAF2, SDHB, SDHC, SDHD, SMARCA4, SPINK1, SPRED1, TMEM127, TSC1, TSC2, VHL, XRCC2

8 Hereditary Cancer Gene Panel Testing Supreme Court overturns BRCA1/2 patent (June 13, 2013) 11/9/2015 8

9 Hereditary Cancer Gene Panel Testing Supreme Court overturns BRCA1/2 patent (June 13, 2013) Flood of commercial laboratories offering testing Next-generation sequencing technology Simultaneous analysis of multiple genes (phenotype specific or pan-cancer) Low cost Initially used for affected BRCA-negative Increasingly used as front-line testing More than one gene could explain phenotype 11/9/2015 9

10 Hereditary Cancer Gene Panel Testing Opportunity for more comprehensive hereditary cancer assessment Mixed family cancer phenotype Increased positive results yield Increasing targeted treatment options Re-testing patients who were previously singlegene negative 11/9/

11 Hereditary Cancer Gene Panel Testing Time- efficiency Surgical decision patients Cost-efficiency Decrease in testing fatigue 11/9/

12 Hereditary Cancer Gene Panel Testing Results interpretation uncertainty Moderate penetrance and limited evidence genes Degree of cancer risks, management Variants of unknown significance Incidental findings 11/9/

13 Hereditary Cancer Gene Panel Testing Insurance coverage and contracts Choice of laboratory and specific panel Consensus of genes per cancer-panel 11/9/

14 Hereditary Cancer Gene Panel Testing Choice of laboratory and specific panel 11/9/

15 Hereditary Cancer Gene Panel Testing Choice of laboratory and specific panel 11/9/

16 Genetic Counseling is a Multistep Process 11/9/

17 Pre-test Genetic Counseling Traditional cancer genetic counseling Genetic education, specific gene risk, management recommendations, potential risks New approaches to genetic counseling and informed consent Single syndrome multi-gene Tiered-binned counseling Style/approach not necessarily consistent among practices or even genetic counselors 11/9/

18 Pre-test Genetic Counseling Specific information for each gene not discussed Tiered information: genes can identify risk High-risk genes vs moderate penetrance Provide patients with reading materials regarding the genes analyzed/risks associated Binned discussion of management Breast, colorectal, gynecologic, etc. Screening vs prophylactic surgery Possible gene-specific discussion? 11/9/

19 Pre-test Genetic Counseling Limitations of genetic testing Uninformative results Inconclusive results / variants of unknown significance Incidental findings Risks of testing Psychological / social risks More specific and comprehensive information may be available at results Testing is voluntary 11/9/

20 Genetic Counseling is a Multistep Process 11/9/

21 Post-test Genetic Counseling Discussion of moderate-penetrance genes Risks and management Recommendations for family members to test single-site? Discussion of incidental or unexpected highpenetrance genes in families lacking features of syndrome 11/9/

22 Post-test Genetic Counseling Resources for patients Limited data limited support resources PCP/oncologist/surgeon/etc. education for care Prevent inappropriate screening (patient anxiety) Prevent inappropriate risk-reducing surgery Annual patient follow-up/updating 11/9/

23 Hereditary Cancer Gene Panel Testing NCCN Guidelines Version Overview of multi-gene testing multigene testing are ideally offered in the context of professional genetic expertise for pre- and post-test counseling Rainville and Rana (2014) Given the complexity of testing and results interpretation, we recommend testing in centers where genetic counseling is provided to enable family history assessment and where patients can be followed and managed over a long term American Society of Clinical Oncology Policy Statement Update (2015) Because of the current uncertainties and knowledge gaps, providers with particular expertise in cancer risk assessment should be involved in the ordering and interpretation of multigene panels that include genes of uncertain clinical utility and genes not suggested by the patient s personal and/or family history 11/9/

24 References National Comprehensive Cancer Network Guidelines Version ; Genetic/Familial High-Risk Assessment: Breast and Ovarian National Comprehensive Cancer Network Guidelines Version ; Genetic/Familial High-Risk Assessment: Colorectal Robson ME et al. American Society of Clinical Oncology Policy Statement Update: Genetic and Genomic Testing for Cancer Susceptibility. J Clin Oncol Off J Am Soc Clin Oncol. 2015; 33(31): Rainville IR, Rana HQ. Next-generation sequencing for inherited breast cancer risk: Counseling through the complexity. Curr Oncol Rep. 2014; 16(371). Slavin TP et al. Clinical applicaition of multigene panels: challenges of nextgeneration counseling and cancer risk management. Front Oncol. 2015; 5(208). Bradbury AR et al. Development of a tiered and binned genetic counseling model for informed consent in the era of multiplex testing for cancer susceptibility. Genetics in Medicine. 2015;7(6). Michigan Department of Health and Human Services. Informed Consent for Genetic Counseling. Updated 8/ /9/